20 games
| Date | Site | Opp AP | Opponent | UL AP | W/L | UL | Opp | OT | Overall | Conf | Attendance | City | State | Arena | Event |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 11/25/2020 | H | Evansville | W | 79 | 44 | 1-0 | 2,956 | Louisville | Ky. | KFC Yum! Center | 2020 Wade Houston Tipoff Classic | ||||
| 11/27/2020 | H | Seton Hall | W | 71 | 70 | 2-0 | 2,988 | Louisville | Ky. | KFC Yum! Center | 2020 Wade Houston Tipoff Classic | ||||
| 11/29/2020 | H | Prairie View A&M | W | 86 | 64 | 3-0 | 2,934 | Louisville | Ky. | KFC Yum! Center | 2020 Wade Houston Tipoff Classic | ||||
| 12/01/2020 | H | Western Kentucky | W | 75 | 54 | 4-0 | 3,013 | Louisville | Ky. | KFC Yum! Center | |||||
| 12/19/2020 | A | 12 | Wisconsin | 23 | L | 48 | 85 | 4-1 | 0 | Madison | Wisc. | Kohl Center | 2020 ACC-Big Ten Challenge | ||
| 12/22/2020 | A | Pittsburgh | W | 64 | 54 | 5-1 | 1-0 | 0 | Pittsburgh | Pa. | Petersen Events Center | ||||
| 12/26/2020 | H | Kentucky | W | 62 | 59 | 6-1 | 1-0 | 3,281 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/02/2021 | A | Boston College | W | 76 | 64 | 7-1 | 2-0 | 0 | Chestnut Hill | Mass. | Conte Forum | ||||
| 01/06/2021 | H | 19 | Virginia Tech | W | 73 | 71 | 8-1 | 3-0 | 2,966 | Louisville | Ky. | KFC Yum! Center | |||
| 01/13/2021 | A | Wake Forest | 16 | W | 77 | 65 | 9-1 | 4-0 | 71 | Winston-Salem | N.C. | Lawrence Joel Veterans Memorial Coliseum | |||
| 01/16/2021 | A | Miami, Fla. | 16 | L | 72 | 78 | 9-2 | 4-1 | 0 | Coral Gables | Fla. | Watsco Center | |||
| 01/18/2021 | H | Florida State | L | 65 | 78 | 9-3 | 4-2 | 3,024 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/23/2021 | H | Duke | W | 70 | 65 | 10-3 | 5-2 | 3,219 | Louisville | Ky. | KFC Yum! Center | ||||
| 01/27/2021 | A | Clemson | 25 | L | 50 | 54 | 10-4 | 5-3 | 1,876 | Clemson | S.C. | Littlejohn Coliseum | |||
| 02/01/2021 | H | Georgia Tech | W | 74 | 58 | 11-4 | 6-3 | 2,868 | Louisville | Ky. | KFC Yum! Center | ||||
| 02/20/2021 | A | North Carolina | L | 54 | 99 | 11-5 | 6-4 | 0 | Chapel Hill | N.C. | Dean E. Smith Center | ||||
| 02/23/2021 | H | Notre Dame | W | 69 | 57 | 12-5 | 7-4 | 2,948 | Louisville | Ky. | KFC Yum! Center | ||||
| 02/27/2021 | A | Duke | W | 80 | 73 | OT | 13-5 | 8-4 | 0 | Durham | N.C. | Cameron Indoor Stadium | |||
| 03/06/2021 | H | 21 | Virginia | L | 58 | 68 | 13-6 | 8-5 | 4,812 | Louisville | Ky. | KFC Yum! Center | |||
| 03/10/2021 | N | Duke | L | 56 | 70 | 13-7 | 8-5 | 0 | Greensboro | N.C. | Greensboro Coliseum | 2021 New York Life ACC Tournament Second Round |